Serum Pepsinogens and Their Comparison with Endoscopic and Histologic Results for Gastric Mucosa in Relatives of Gastric Cancer Patients

Study Objective: to study the possibility of using serological markers pepsinogen 1 (PG-1), pepsinogen 2 (PG-2) and their ratio in pre-cancer screening in genetic heredity of gastric cancer (GC), in relatives of GC patients. Materials and Methods. The study included 114 relatives of GC patients (study group) and 117 patients without family history of GC who were examined for dyspepsia (controls). All subjects underwent clinical examination, questionnaire survey and esophagogastroduodenoscopy with biopsy to assess the gastric mucosa status in accordance with the modified Sydney System, OLGA and OLGIM systems, and had Helicobacter pylori infection assessed. PG-1, PG-2 and their ratio were measured in blood serum. Pepsinogen test (PT) results were used to distribute the subjects (226 individuals, 5 were excluded) into three groups: negative PT (nPT) (PG-1 > 70 ng/mL and PG-1/2 > 3.0); controversal PT (cPT) (PG-1 ≤ 70 ng/mLor PG-1/2 ≤ 3.0); positive PT (pPT) (PG-1 ≤ 70 ng/mL and PG-1/2 ≤ 3.0). Study Results. Relatives of GC patients vs. controls had more frequent atrophy of any location (49.1 vs. 23.9%, p = 0.000), antral gastratrophia (43.9% vs. 23.1%, p = 0.000). Metaplasia (any location) in relatives of GC patients was also more common vs. controls (22.8% vs. 12.8%; p = 0.047). Incidence of H. pylori in test group was 57.9%, in controls it was 53.9%. In relatives of GC patients, atrophy had earlier onset (45.9 vs. 54.7 years old in controls; p < 0.001). Analysis of PT results revealed the association between pPT and overweight (85.2% vs. 57.7% in cPT and 55.2% in nPT; p = 0.024), age (37.3 years in pPT vs. 39.1 years in cPT and 49 years in nPT; p = 0.002), and family history of GC (66.7% vs. 51.3% in cPT and 44.6% in nPT; p = 0.043). Also, PT results depended on any atrophy (nPT — 28.9%, cPT — 41.0%, pPT — 62.9%; p = 0.001), particularly on antral atrophy (nPT — 28.1%, cPT — 37.2%, pPT — 51.9%; p = 0.015). Gastritis stages I–IV as per OLGA were found in 28.9% of nPT subjects, in 41.0% of cPT subjects, and 63.0% in pPT subjects. When gastritis metaplasia severity as per OLGIM was assessed, we found significant increase in the number of I-II stage cases in cPT (19.2%) and pPT (37.0%) groups vs. nPT group (9.1%) (p = 0.003). Multivariate analysis demonstrated the following atrophy risk factors (serological PT results): family history of gastric cancer (RR = 1.6; 95% CI: 1.0–2.8; p = 0.037), overweight (BMI > 25 kg/m2) (RR = 2.1; 95% CI: 1.3–3.7; p = 0.003), marked gastric inflammation (stage 2–3) (RR = 1.8; 95% CI: 1.1–3.0; p = 0.018), and metaplasia (of any location) (RR = 2.3; 95% CI: 1.2–4.5; p = 0.008). Conclusion. A non-invasive assessment of gastric mucosa changes using H. pylori antibody and blood PG-1 tests is a promising method. However, serological PTs should be studied across various populations and regions. Keywords: screening, family history, gastric cancer, chronic gastratrophia, metaplasia, pepsinogen.